目的:总结1例新生儿X连锁中央核肌病临床及遗传学特征并进行文献复习。方法:回顾性分析2024年4月临沂市妇幼保健院新生儿监护室收治的1例诊断为X连锁中央核肌病患儿的临床资料,并复习相关文献。结果:男性患儿,胎龄34+1周出生,有出生窒...目的:总结1例新生儿X连锁中央核肌病临床及遗传学特征并进行文献复习。方法:回顾性分析2024年4月临沂市妇幼保健院新生儿监护室收治的1例诊断为X连锁中央核肌病患儿的临床资料,并复习相关文献。结果:男性患儿,胎龄34+1周出生,有出生窒息史。头围大,隐睾,肌张力低,存在呼吸及吞咽功能障碍,最终家长放弃后死亡。全外显子测序发现MTM1基因存在无义突变c.70C>T:p.Arg24*,结合患儿临床特点,确诊为X连锁中央核肌病(X-linked myotubular myopathy, XLMTM)。家系验证变异为新发变异。复习文献及检索数据库发现目前国内报道的MTM1突变所致XLMTM病例较少,近5年来共18例,国外相对较多。MTM1-Leiden开放数据库截止到2024年4月29日,共发现568名变异个体的598个变异位点。国内外报道该类肌病多数表型较严重,常在新生儿期发病并在婴儿期死亡。结论:通过临床资料及基因分析确诊了1例新生儿期发病的X连锁中央核肌病,基因分析证实了MTM1基因c.70C>T:p.Arg24*为该患儿的致病突变,该突变为国内外首次报道,拓展了MTM1基因的突变谱。Objective: To summarize the clinical and genetic characteristics of a neonatal X-linked myotubular myopathy and review the literature. Methods: The clinical data of a case diagnosed with X-linked myotubular myopathy admitted to the neonatal care unit of Woman and Children’s Healthcare Hospital of Linyi in April 2024 were retrospectively analyzed, and the relevant literature was also reviewed. Results: The male infant was born with a gestational age of 34+1 weeks and had a history of birth asphyxia. He had a large head circumference, cryptorchidism, low muscle tone, respiratory and swallowing dysfunction, and eventually died after his parents gave up. Whole-exome sequencing found a nonsense mutation c.70C>T:p.Arg24* in the MTM1 gene. Based on the clinical characteristics of the child, the patient was diagnosed with X-linked myotubular myopathy (XLMTM). Family validation showed that the mutation was a new occurrence. Reviewing the literature and searching the database found that there are currently few cases of XLMTM caused by MTM1 mutations reported in China, with a total of 18 cases in the past five years, and relatively many cases abroad. As of April 29, 2024, the MTM1-Leiden open database has found a total of 598 mutation sites in 568 mutated individuals. It has been reported at home and abroad that most of the phenotypes of this type of myopathy are severe, often onset in the neonatal period and death in infancy. Conclusion: A case of neonatal-onset X-linked myotubular myopathy was diagnosed by clinical data and genetically confirmed, and the MTM1 gene c.70C>T:p.Arg24* was genetically confirmed to be the causative mutation in this child, which is the first report in China and abroad, and expands the spectrum of mutations in the MTM1 gene.展开更多
文摘目的:总结1例新生儿X连锁中央核肌病临床及遗传学特征并进行文献复习。方法:回顾性分析2024年4月临沂市妇幼保健院新生儿监护室收治的1例诊断为X连锁中央核肌病患儿的临床资料,并复习相关文献。结果:男性患儿,胎龄34+1周出生,有出生窒息史。头围大,隐睾,肌张力低,存在呼吸及吞咽功能障碍,最终家长放弃后死亡。全外显子测序发现MTM1基因存在无义突变c.70C>T:p.Arg24*,结合患儿临床特点,确诊为X连锁中央核肌病(X-linked myotubular myopathy, XLMTM)。家系验证变异为新发变异。复习文献及检索数据库发现目前国内报道的MTM1突变所致XLMTM病例较少,近5年来共18例,国外相对较多。MTM1-Leiden开放数据库截止到2024年4月29日,共发现568名变异个体的598个变异位点。国内外报道该类肌病多数表型较严重,常在新生儿期发病并在婴儿期死亡。结论:通过临床资料及基因分析确诊了1例新生儿期发病的X连锁中央核肌病,基因分析证实了MTM1基因c.70C>T:p.Arg24*为该患儿的致病突变,该突变为国内外首次报道,拓展了MTM1基因的突变谱。Objective: To summarize the clinical and genetic characteristics of a neonatal X-linked myotubular myopathy and review the literature. Methods: The clinical data of a case diagnosed with X-linked myotubular myopathy admitted to the neonatal care unit of Woman and Children’s Healthcare Hospital of Linyi in April 2024 were retrospectively analyzed, and the relevant literature was also reviewed. Results: The male infant was born with a gestational age of 34+1 weeks and had a history of birth asphyxia. He had a large head circumference, cryptorchidism, low muscle tone, respiratory and swallowing dysfunction, and eventually died after his parents gave up. Whole-exome sequencing found a nonsense mutation c.70C>T:p.Arg24* in the MTM1 gene. Based on the clinical characteristics of the child, the patient was diagnosed with X-linked myotubular myopathy (XLMTM). Family validation showed that the mutation was a new occurrence. Reviewing the literature and searching the database found that there are currently few cases of XLMTM caused by MTM1 mutations reported in China, with a total of 18 cases in the past five years, and relatively many cases abroad. As of April 29, 2024, the MTM1-Leiden open database has found a total of 598 mutation sites in 568 mutated individuals. It has been reported at home and abroad that most of the phenotypes of this type of myopathy are severe, often onset in the neonatal period and death in infancy. Conclusion: A case of neonatal-onset X-linked myotubular myopathy was diagnosed by clinical data and genetically confirmed, and the MTM1 gene c.70C>T:p.Arg24* was genetically confirmed to be the causative mutation in this child, which is the first report in China and abroad, and expands the spectrum of mutations in the MTM1 gene.
